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Atherosclerotic disease of the carotid arteries is a crucial risk factor in predicting the likelihood of future stroke events. In addition, emerging studies suggest that carotid stenosis may also be an indicator of plaque load on coronary arteries and thus have a correlation with the risk of acute cardiovascular events. Furthermore, although in symptomatic patients the degree of stenosis is the main morphological parameter studied, recent evidence suggests, especially in asymptomatic patients, that plaque vulnerability should also be evaluated as an emerging and significant imaging parameter. The reference diagnostic methods for the evaluation of carotid stenosis are currently ultrasonography, magnetic resonance imaging (MRI), and computed tomography angiography (CTA). In addition, other more invasive methods such as 123I-metaiodobenzylguanidine (MIBG) scintigraphy and PET-CT, as well as digital subtraction angiography, can be used. Each method has advantages and disadvantages, and there is often some confusion in their use. For example, the usefulness of MRI is often underestimated. In addition, implementations for each method have been developed over the years and are already enabling a significant increase in diagnostic accuracy. The purpose of our study is to make an in-depth analysis of all the methods in use and in particular their role in the diagnostic procedure of carotid stenosis, also discussing new technologies.

Plant trade and exchange for horticulture, recreation or research play a significant role in the dispersal of molluscs. Alien slugs and snails accidentally introduced into Europe have established rich communities in several countries, but although these introductions could have ecological and economic implications, mollusc xenodiversity in Italian botanical gardens, plant nurseries, and greenhouses has never been investigated. Facilities throughout the country were therefore visited between 2017 and 2023. Here the list of the achatinoidean species so far recorded from Italian greenhouses is provided, giving a short description of their diagnostic characters. The greenhouses of Trento and Padua host interesting assemblages of achatinoideans: the results of this study include the first reports of four achatinids, namely Allopeasclavulinum , Opeashannense , Paropeasachatinaceum and Subulinaoctona from Italy and the first record of Geostilbiaaperta from Europe. Reproductive anatomy of all species except Geostilbiaaperta is illustrated in detail, integrating anatomical knowledge of this group of tiny molluscs, some of which are known mainly from their shell characters. The systematics of all the species is discussed, highlighting topics for future research (e.g., status of Allopeasmauritianum , real identity of Helixhannense , anatomy of Opeashannense , species-level taxonomy of Subulina , systematic relationships and species-level taxonomy of Geostilbia )., Competing Interests: The authors have declared that no competing interests exist., (Giuseppe Manganelli, Andrea Benocci, Debora Barbato, Folco Giusti.)

Ultrasound (US) is the primary tool for evaluating patients with thyroid nodules, and the risk of malignancy assessed is based on US features. These features help determine which patients require fine-needle aspiration (FNA) biopsy. Classification systems for US features have been developed to facilitate efficient interpretation, reporting, and communication of thyroid US findings. These systems have been validated by numerous studies and are reviewed in this article. Additionally, this overview provides a comprehensive description of the clinical and laboratory evaluation of patients with thyroid nodules, various imaging modalities, grayscale US features, color Doppler US, contrast-enhanced US (CEUS), US elastography, FNA biopsy assessment, and the recent introduction of molecular testing. The potential of artificial intelligence in thyroid US is also discussed.

Emergency imaging in pregnancy and puerperium poses unique challenges both for clinicians and radiologists, requiring timely and accurate diagnosis. Delay in treatment may result in poor outcomes for both the patient and the foetus. Pregnant and puerperal patients may present in the emergency setting with acute abdominopelvic pain for various complications that can be broadly classified into obstetric and non-obstetric related diseases. Ultrasonography (US) is the primary diagnostic imaging test; however, it may be limited due to the patient's body habitus and the overlapping of bowel loops. Computed tomography (CT) carries exposure to ionising radiation to the foetus, but may be necessary in selected cases. Magnetic resonance imaging (MRI) is a valuable complement to US in the determination of the etiology of acute abdominal pain and can be used in most settings, allowing for the identification of a broad spectrum of pathologies with a limited protocol of sequences. In this second section, we review the common non-obstetric causes for acute abdominopelvic pain in pregnancy and post partum, offering a practical approach for diagnosis and pointing out the role of imaging methods (US, MRI, CT) with the respective imaging findings.

Acute abdominopelvic pain in pregnant and postpartum patients presents clinical and therapeutic challenges, often requiring quick and accurate imaging diagnosis. Ultrasound remains the primary imaging investigation. Magnetic resonance imaging (MRI) has been shown to be a powerful diagnostic tool in the setting of acute abdominal pain during pregnancy and puerperium. MRI overcomes some drawbacks of US, avoiding the ionizing radiation exposure of a computed tomography (CT) scan. Although CT is not usually appropriate in pregnant patients, it is crucial in the emergency evaluation of postpartum complications. The aim of this article is to provide radiologists with a thorough familiarity with the common and uncommon pregnancy and puerperium abdominal emergencies by illustrating their imaging appearances. The present first section will review and discuss the imaging findings for acute abdominopelvic pain of obstetric (non-fetal) etiology.

Cervical cancer (CC) is the fourth leading cause of death in women worldwide and despite the introduction of screening programs about 30% of patients presents advanced disease at diagnosis and 30-50% of them relapse in the first 5-years after treatment. According to FIGO staging system 2018, stage IB3-IVA are classified as locally advanced cervical cancer (LACC); its correct therapeutic choice remains still controversial and includes neoadjuvant chemo-radiotherapy, external beam radiotherapy, brachytherapy, hysterectomy or a combination of these modalities. In this review we focus on the most appropriated therapeutic options for LACC and imaging protocols used for its correct follow-up. We explore the imaging findings after radiotherapy and surgery and discuss the role of imaging in evaluating the response rate to treatment, selecting patients for salvage surgery and evaluating recurrence of disease. We also introduce and evaluate the advances of the emerging imaging techniques mainly represented by spectroscopy, PET-MRI, and radiomics which have improved diagnostic accuracy and are approaching to future direction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ciulla, Celli, Aiello, Gigli, Ninkova, Miceli, Ercolani, Dolciami, Ricci, Palaia, Catalano and Manganaro.)

Objectives: The recommendations cover indications for MRI examination including acquisition planes, patient preparation, imaging protocol including multi-parametric approaches such as diffusion-weighted imaging (DWI-MR),  dynamic contrast-enhanced imaging (DCE-MR) and standardised reporting. The document also underscores the value of whole-body 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) and highlights potential future methods., Methods: In 2019, the ESUR female pelvic imaging working group reviewed the revised 2018 FIGO staging system, the up-to-date clinical management guidelines, and the recent imaging literature. The RAND-UCLA Appropriateness Method (RAM) was followed to develop the current ESUR consensus guidelines following methodological steps: literature research, questionnaire developments, panel selection, survey, data extraction and analysis., Results: The updated ESUR guidelines are recommendations based on ≥ 80% consensus among experts. If ≥ 80% agreement was not reached, the action was indicated as optional., Conclusions: The present ESUR guidelines focus on the main role of MRI in the initial staging, response monitoring and evaluation of disease recurrence. Whole-body FDG-PET plays an important role in the detection of lymph nodes (LNs) and distant metastases., Key Points: • T2WI and DWI-MR are now recommended for initial staging, monitoring of response and evaluation of recurrence. • DCE-MR is optional; its primary role remains in the research setting. • T2WI, DWI-MRI and whole-body FDG-PET/CT enable comprehensive assessment of treatment response and recurrence., (© 2020. European Society of Radiology.)

Purpose:  To evaluate the diagnostic performance of strain elastography (SE) and 2 D shear wave elastography (SWE) and SE/SWE combination in comparison with conventional multiparametric ultrasound (US) with respect to improving BI-RADS classification results and differentiating benign and malignant breast lesions using a qualitative and quantitative assessment., Materials and Methods:  In this prospective study, 130 histologically proven breast masses were evaluated with baseline US, color Doppler ultrasound (CDUS), SE and SWE (Toshiba Aplio 500 with a 7-15 MHz wide-band linear transducer). Each lesion was classified according to the BIRADS lexicon by evaluating the size, the B-mode and color Doppler features, the SE qualitative (point color scale) and SE semi-quantitative (strain ratio) methods, and quantitative SWE. Histological results were compared with BIRADS, strain ratio (SR) and shear wave elastography (SWE) all performed by one investigator blinded to the clinical examination and mammographic results at the time of the US examination. The area under the ROC curve (AUC) was calculated to evaluate the diagnostic performance of B-mode US, SE, SWE, and their combination., Results:  Histological examination revealed 47 benign and 83 malignant breast lesions. The accuracy of SR was statistically significantly higher than SWE (sensitivity, specificity and AUC were 89.2 %, 76.6 % and 0.83 for SR and 72.3 %, 66.0 % and 0.69 for SWE, respectively, p = 0.003) but not higher than B-mode US (B-mode US sensitivity, specificity and AUC were 85.5 %, 78.8 %, 0.821, respectively, p = 1.000)., Conclusion:  Our experience suggests that conventional US in combination with both SE and SWE is a valid tool that can be useful in the clinical setting, can improve BIRADS category assessment and may help in the differentiation of benign from malignant breast lesions, with SE having higher accuracy than SWE., Competing Interests: Cantisani: Speaker, Canon Medical Systems Corporation, Speaker, Bracco Group, Speaker, Samsung Electronics Co, Ltd; Barr: Consultant, Siemens AG Speakers Bureau, Siemens AG Research Grant, Siemens AG Consultant, Koninklijke Philips NV Speakers Bureau, Koninklijke Philips NV Consultant, Canon Medical Systems Corporation Research Grant, SuperSonic Imagine Research Grant, Bracco Group Research Grant, Esaote SpA Research Grant, BK Ultrasound Research Grant, Hitachi, Ltd; Radzina: Lecturer honoraria (Bayer, Canon, Bracco); Pediconi: Lecturer (bracco, Bayer, Siemens)., (Thieme. All rights reserved.)

Y RNA are a class of small non-coding RNA that are largely conserved. Although their discovery was almost 40 years ago, their function is still under investigation. This is evident in cancer biology, where their role was first studied just a dozen years ago. Since then, only a few contributions were published, mostly scattered across different tumor types and, in some cases, also suffering from methodological limitations. Nonetheless, these sparse data may be used to make some estimations and suggest routes to better understand the role of Y RNA in cancer formation and characterization. Here we summarize the current knowledge about Y RNA in multiple types of cancer, also including a paragraph about tumors that might be included in this list in the future, if more evidence becomes available. The picture arising indicates that Y RNA might be useful in tumor characterization, also relying on non-invasive methods, such as the analysis of the content of extracellular vesicles (EV) that are retrieved from blood plasma and other bodily fluids. Due to the established role of Y RNA in DNA replication, it is possible to hypothesize their therapeutic targeting to inhibit cell proliferation in oncological patients.

The World Health Organization (WHO) defines infertility as the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy within one year. Statistics show that the two sexes are equally at risk. Several causes may be responsible for male infertility; however, in 30-40% of cases a diagnosis of idiopathic male infertility is made in men with normal urogenital anatomy, no history of familial fertility-related diseases and a normal panel of values as for endocrine, genetic and biochemical markers. Idiopathic male infertility may be the result of gene/environment interactions, genetic and epigenetic abnormalities. Numerical and structural anomalies of the Y chromosome represent a minor yet significant proportion and are the topic discussed in this review. We searched the PubMed database and major search engines for reports about Y-linked male infertility. We present cases of Y-linked male infertility in terms of (i) anomalies of the Y chromosome structure/number; (ii) Y chromosome misbehavior in a normal genetic background; (iii) Y chromosome copy number variations (CNVs). We discuss possible explanations of male infertility caused by mutations, lower or higher number of copies of otherwise wild type, Y-linked sequences. Despite Y chromosome structural anomalies are not a major cause of male infertility, in case of negative results and of normal DNA sequencing of the ascertained genes causing infertility and mapping on this chromosome, we recommend an analysis of the karyotype integrity in all cases of idiopathic fertility impairment, with an emphasis on the structure and number of this chromosome.

Introduction: To determine the performance of texture analysis and conventional MRI parameters in predicting tumoral response to neoadjuvant chemotherapy and to assess whether a relationship exists between texture tissue heterogeneity and histological type of uterine cervix cancer., Method and Materials: Twenty-eight patients with local advanced cervical cancer (FIGO IB2-IIIB), underwent MRI before chemotherapy. Texture analysis parameters were quantified on T2-weighted sequences, as well as the maximum diameter expressed in mm. ADC values were obtained on the ADC map. Statistical analysis included unpaired t test and ROC curve., Results: No statistical correlation was found between conventional parameters and response to NACT. Mean and skewness showed a strong correlation with the histological type: Adenocarcinomas presented higher mean and skewness values (69.8 ± 10.5 and 0.55 ± 0.19) in comparison with squamous cell carcinomas. Using a cutoff value ≥ 29 for mean it was possible to differentiate the two histological types with a sensitivity of 100% and a specificity of 81%. Kurtosis showed a positive correlation with tumor response to NACT resulting higher in responders (v.m. 5.7 ± 1.1) in comparison with non-responders (2.3 ± 0.5). The optimal Kurtosis cutoff value for the identification of non-responders tumors was ≤ 3.7 with a sensitivity of 92% and a specificity of 75%., Conclusion: Texture analysis applied to T2-weighted images of uterine cervical cancer exceeded the role of conventional prognostic factors in predicting tumoral response; moreover, they showed a potential role to differentiate histological tumor types.

Because histamine is a modulator of cancer cell proliferation and invasiveness, this study aimed at investigating the effect of Lathyrus sativus-derived diamine oxidase (LSAO) and its mechanism of action on Caco-2 cell line, considering that LSAO catalizes the oxidative deamination of histamine to the corresponding aldehyde, NH 3 and H 2 O 2 . Histamine (0.01-1 μM) caused a proliferative effect on Caco-2 cells promoting cell migration, invasion and nitric oxide and vascular endothelial growth factor release. Histamine (1 μM) stimulus also down regulated occludin expression, favouring up regulation of pro-proliferative nuclear protein Ki67. Incubation with LSAO (0.004-0.4 μM) resulted in a significant inhibition of histamine-induced effects. LSAO rescued occludin expression and down regulated Ki67, and it inhibited histamine-induced increase of both MMP-2 and 9 expression. Histamine effects were mediated by RhoA-GTP down regulation and inversely related to phospho-p38MAPK/p50/65 up regulation. These effects were counteracted by LSAO incubation. Histamine catabolism by LSAO accounts for a significant down regulation of proliferation and invasiveness of Caco-2 cells. This study highlights the importance to control histamine levels in contrasting pro-angiogenic and metastatization capability of colon cancer cells and expands the knowledge about the diamine oxidase from L. sativus seeding as a phytotherapeutic approach for colon cancer., (© 2019 John Wiley & Sons, Ltd.)

Rationale and Objectives: The aim of this study was to retrospectly investigate the association between different breast cancer (BC) immunohistochemical subtypes and morphological and semiquantitative kinetic analysis on breast magnetic resonance imaging (MRI) performed before surgery treatment. Specifically we aimed to assess MRI features of triple-negative breast cancer (TNBC) compared to the other BC subtypes (nTNBC)., Materials and Methods: Patients undergone to breast MRI and then diagnosed with BC by core-needle biopsy were included. The MRI morphological and kinetic features were studied. Parametric and non-parametric tests were used, as appropriate., Results: Seventy-five BC patients were considered, 30 patients included in TNBC Group and 45 patients included in nTNBC Group. We found in TNBC Group a greater mean lesion size (P <0.001), a rim enhancement imaging (P=0.003), and a higher intratumoral signal intensity on T2-weighted images (P=0.03) with respect to nTNBC Group. We noticed that TNBC patients presented a lower grade of BPE when compared to the nTBC Group (P< 0.02). TNBC Group showed lower EPeak values (P=0.003) and higher SER values (P=0.02) with respect to the nTNBC Group. In addition, stratifying kinetics parameters according to the tumor grade, the TNBC Group presented higher tumor grade (G3) (P< 0.005) and this subgroup had higher SER values when compared to TNBCs showing a lower tumor grade (G1 and G2) (P=0.03)., Conclusion: After validation by large-scale studies, the morphological and semiquantitative kinetic analysis on dynamic contrast enhanced MRI may help in the pretreatment risk stratification of patients with TNBC and in evidence-based clinical decision support., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Ovarian cancer is one of the most aggressive gynaecologic malignancies in women worldwide. The lack of proper screening programs and the characteristic abdominal spreading with minimal clinical symptoms give rise of its high lethality. Most patients show advanced disease at diagnosis and have a poor prognosis. The surveillance of ovarian cancer patients after initial treatment is a challenging question in clinical practice and there is no consensus in literature about the most appropriate follow-up strategy for these women. The role of Imaging has become increasingly important, allowing to properly monitor patients, distinguishing the different relapse patterns, thus guiding the correct management and therapy. In this review, we report and analyze the scientific evidence about the role of the different imaging modalities now available in the follow-up strategy and management of Epithelial Ovarian Cancer patients with recurrent disease.

Preclinical and clinical evidences have demonstrated that astroglial-derived S100B protein is a key element in neuroinflammation underlying the pathogenesis of Parkinson's disease (PD), so much as that S100B inhibitors have been proposed as promising candidates for PD targeted therapy. Pentamidine, an old-developed antiprotozoal drug, currently used for pneumocystis carinii is one of the most potent inhibitors of S100B activity, but despite this effect, is limited by its low capability to cross blood brain barrier (BBB). To overcome this problem, we developed a non-invasive intranasal delivery system, chitosan coated niosomes with entrapped pentamidine (inPentasomes), in the attempt to provide a novel pharmacological approach to ameliorate parkinsonism induced by subchronic MPTP administration in C57BL-6 J mice. inPentasomes, prepared by evaporation method was administered daily by intranasal route in subchronic MPTP-intoxicated rodents and resulted in a dose-dependent manner (0.001-0.004 mg/kg) capable for a significant Tyrosine Hydroxylase (TH) positive neuronal density rescue in both striatum and substantia nigra of parkinsonian mice. In parallel, inPentasomes significantly decreased the extent of glial-related neuroinflammation through the reduction of specific gliotic markers (Iba-1, GFAP, COX-2, iNOS) with consequent PGE 2 and NO 2 - release reduction, in nigrostriatal system. inPentasomes-mediated S100B inhibition resulted in a RAGE/NF-κB pathway downstream inhibition in the nigrostriatal circuit, causing a marked amelioration of motor performances in intoxicated mice. On the basis of our results, chitosan coated niosomes loaded with pentamidine, the inPentasome system, self-candidates as a promising new intranasal approach to mitigate parkinsonism in humans and possibly paves the way for a possible clinical repositioning of pentamidine as anti-PD drug., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Universal health coverage reforms are complex and impact numerous processes, institutions, and individuals. To know whether reforms are being implemented as planned and working as envisioned, policy makers and managers need information and insights on bottlenecks. The United States Agency for International Development (USAID) provided support to build implementation research (IR) capacity and to conduct cycles of research to help Indonesia understand how its single-payer national insurance reform, Jaminan Kesehatan Nasional (JKN), was affecting primary care. Two cycles of IR in Indonesia focused on effects of JKN financing on primary care, as determined through a consultative process with stakeholders at national and district levels. This process generated questions relevant for implementers and policy makers and strengthened government interest in findings. Research was conducted in 5 diverse districts, and methods included key informant interviews, focus groups, document review, health worker surveys, and analysis of service delivery data. Cycle 1 findings showed an uneven understanding of JKN regulations, unequal implementation readiness, and limited evidence of improved productivity. JKN capitation payments did not increase health worker satisfaction or motivate additional effort. Informed by these findings, regulations were rewritten and the capitation payment formula was redesigned to include payment conditional on performance. Cycle 2 found that health workers experienced increased workloads because of increased enrollment in JKN and the requirement that people access primary care before being referred to higher levels of care. In addition, health workers indicated they did not experience the payment system to be fair. Instead of payment being conditional on performance, they indicated it was primarily determined by education and tenure, with only some districts incorporating a small payment component based on behaviors, such as attendance, and performance. The health workers said they preferred to be paid based on achieving primary care targets. Conducting IR so that questions are relevant and the process of finding and sharing answers is timely and cost-effective requires high-level skills, but support to build IR capacity has potential to make a lasting impact., (© Eichler et al.)

Diagnostic ultrasound (US) images can be obtained from a quality device, in optimal working conditions, combined with the capable actions of the operator in tweaking the equipment's characteristics. The quality assurance (QA) is the topic of this review article, and it is addressed in an US practice through proper selection of the equipment when purchasing, and through care and preventive maintenance of the machine for ensuring accurate performance. For optimal US system functioning, QA steps carried out on the basis of a scheduled program are needed in any US practice or department. It is critical to confirm in a semiannual or annual basis that the image quality is maintained according to standards and any subtle change in equipment's functioning is detected and amended at an early stage. The use of test objects (also called US testing phantoms) is required above the basic level of QA testing. The scope of this review article is to inform the US user about necessary QA knowledge and at the same time, present the state of the art of the most suitable test methods for US QA. We referred to relevant publications, selected after performing a systematic literature search of the MEDLINE, EMBASE and COCHRANE databases, and also to the standards established by authoritative international societies.

Objective: We provide a review of the literature about the Androgen Insensitivity Syndrome (AIS), its onset and associated developmental anomalies and the genetic alterations causing it., Materials and Methods: We searched PubMed with a larger emphasis on the physiology, genetics and current management of AIS., Results: AIS is an X-linked recessive Disorder of Sex Development (DSD). It is caused by mutations of the Androgen Receptor, and their large amount and heterogeneity (missense and nonsense mutations, splicing variants, deletions, and insertions) are responsible for the wide spectrum of possible phenotypes of patients, divided into Partial AIS (PAIS) and Complete AIS (CAIS). Once the clinical and laboratory investigations have laid the foundation for a diagnostic hypothesis, it is important to identify the actual karyotype of the individual and search for the mutation in the Androgen Receptor to diagnose with certainty the syndrome. Alternatively, in the absence of such evidence, the diagnosis should more properly be an AIS-like condition, which we describe as well in our report., Conclusions: The management of this DSD is based on pharmacotherapies, surgery and psychological support: all of them must be directed to facilitate the patient's life, considering his/her sexual identity.

The management of end-of-life tyres (ELTs) is regulated by several national and international legislations aiming to promote the recovery of materials and energy from this waste. The three main materials used in tyres are considered: rubber (main product), which is currently reused in other closed-loop applications; steel, which is used for the production of virgin materials; and textile fibres (approximately 10% by weight of ELTs), which are mainly incinerated for energy recovery (open-loop scenario). This study aims to propose and validate a new closed-loop scenario for textile fibres based on material reuse for bituminous conglomerates. The final objective is to verify the technical, environmental, financial, and economic feasibility of the proposed treatment process and reuse scenario. After characterization of the textile material, which is required to determine the technological feasibility, a specific process has been developed to clean, compact, and prepare the fibres for subsequent reuse. A life cycle assessment (LCA) has been carried out to quantify the environmental benefits of reusing the fibres. Finally, a cost benefit analysis based on the LCA results was conducted to establish the long-term financial and economic sustainability. From a technological point of view, the tyre textile fibres could be a promising substitute to the reinforcement cellulose commonly used in asphalts as long as the fibres are properly prepared (compaction and pellet production) for application in the standard bituminous conglomerate production process. From an environmental point of view, relevant benefits in terms of global warming potential and acidification potential reduction were observed in comparison with the standard incineration for energy recovery (respectively -86% and -45%). Moreover, the proposed scenario can be considered as financially viable in the medium to long term (cumulative generated cash flow is positive after the 5th year) and economically sustainable (expected net present value of more than €3,000,000 and economic rate of return of approximately 30%). Finally, the sensitivity and risk analyses show that no specific issues are foreseen for the future implementation in real industrial applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Diarrhea is a severe complication in HIV-1-infected patients with Trans-activator of transcription (HIV-1 Tat) protein being recognized as a major underlying cause. Beside its direct enterotoxic effects, Tat protein has been recently shown to affect enteric glial cell (EGC) activity. EGCs regulate intestinal inflammatory responses by secreting pro-inflammatory molecules; nonetheless, they might also release immune-regulatory factors, as palmytoilethanolamide (PEA), which exerts anti-inflammatory effects by activating PPARα receptors. We aimed at clarifying whether EGCs are involved in HIV-1 Tat-induced diarrhea and if PEA exerts antidiarrheal activity., Methods: Diarrhea was induced by intracolonic administration of HIV-1 Tat protein in rats at day 1. PEA alone or in the presence of peroxisome proliferator-activated receptor (PPAR) antagonists was given intraperitoneally from day 2 to day 7. S100B, iNOS, NF-kappaB, TLR4 and GFAP expression were evaluated in submucosal plexi, while S100B and NO levels were measured in EGC submucosal plexi lysates, respectively. To verify whether PEA effects were PPARα-mediated, PPARα -/- mice were also used. After 7 days from diarrhea induction, endogenous PEA levels were measured in submucosal plexi homogenates deriving from rats and PPARα -/- mice., Results: HIV-1 Tat protein induced rapid onset diarrhea alongside with a significant activation of EGCs. Tat administration significantly increased all hallmarks of neuroinflammation by triggering TLR4 and NF-kappaB activation and S100B and iNOS expression. Endogenous PEA levels were increased following HIV-1 Tat exposure in both wildtype and knockout animals. In PPARα -/- mice, PEA displayed no effects. In wildtype rats, PEA, via PPARα-dependent mechanism, resulted in a significant antidiarrheal activity in parallel with marked reduction of EGC-sustained neuroinflammation., Conclusions: EGCs mediate HIV-1 Tat-induced diarrhea by sustaining the intestinal neuroinflammatory response. These effects are regulated by PEA through a selective PPARα-dependent mechanism. PEA might be considered as an adjuvant therapy in HIV-1-induced diarrhea.

Gynecological tumors, including endometrial, cervical and ovarian cancer, have increased in incidence over time. The widespread introduction of screening programs and advances in diagnostic imaging methods has lead to a progressive increase in gynecological cancer detection. Accurate diagnosis and proper monitoring of disease remain the primary target for a successful treatment. In the last years, knowledge about cancer biomarkers has considerably increased providing great opportunities for improving cancer detection and treatment. In addition, in the last few years there has been an important development of imaging techniques. Nowadays, a multimodal approach including the evaluation of serum tumor biomarkers combined with imaging techniques, seems to be the best strategy for assessing tumor presence, spread, recurrence, and/or the response to treatment in female cancer patients In this review we provide an overview of the application of biomarkers combined with novel imaging methods and highlight their roles in female cancer diagnosis and follow-up., (Creative Commons Attribution License)

The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Clostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity., Objective: The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A., Methods: Caco-2 cells were exposed to Clostridium difficile toxin A (30 ng/ml), with or without cannabidiol (10 -7 -10 -9  M), in the presence of the specific antagonist AM251 (10 -7  M). Cytotoxicity assay, transepithelial electrical resistence measurements, immunofluorescence analysis and immunoblot analysis were performed in the different experimental conditions., Results: Clostridium difficile toxin A significantly decreased Caco-2 cells' viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251., Conclusions: Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.

Objective: Vesicoureteral reflux (VUR) affects up to 1% of Caucasian children. Primary VUR is characterized by failure of the ureterovesicular junction to prevent urine from traveling in a retrograde fashion from the bladder to the ureters and the kidneys. Several reports in the literature describe the prevalence of this condition in pediatric patients; overall, VUR affects more males during infancy and with higher grades. However, a thorough consideration of these articles reveals important contradictions regarding the prevalence by gender and age. We analyzed those contradictions and suggested a possible explanation based on our single center experience with this patient group. In particular, for the age interval 0-2 years: we have found that (1) VUR mostly affects boys; (2) the male/female ratio steadily declines over time; (3) the unequal prevalence between males and females essentially disappears when children reach the age of two years., Conclusions: The natural history of VUR in infant boys differs from that of infant girls, and therefore requires a gender-specific approach. Available data support the need to redefine the categorization and clinical guidelines for this disease.

Breast lipofilling uses autologous fat grafting to correct breast defects after radical or conservative surgery. After early concerns regarding its application in reconstruction after breast cancer (BC), in 2009 the American Society of Plastic Surgeons formed a task force to assess the indications, safety and efficacy of autologous fat grafting. We report the case of a woman who came to our attention for a painful swelling of the left breast. She had undergone breast-conserving therapy for BC, followed by lipofilling. The breast ultrasound (US) examination showed diffuse structural alteration and multiple hypoechoic areas with acoustic shadowing, mainly localized in the subcutaneous tissue. After pharmacological treatment and short-term follow-up US examination, considering the persistence of the clinical symptoms and structural alterations, we performed contrast-enhanced magnetic resonance imaging, that showed multiple enhancing areas in the left breast. Suspecting local tumor recurrence, we carried out US-guided breast core-biopsy, whose histological examination documented liponecrosis. This observation raised a series of diagnostic and therapeutic issues highlighting the diagnostic pitfalls that the radiologist may encounter during the evaluation of patients who have undergone BC surgery and breast reconstruction through lipofilling., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Breast-oncoplastic surgery, allowing local tumor control and a better cosmetic outcome, is oncologically safe when applied to early-stage breast cancer. Breast cancer recurrence following conservative therapy may occur during the first 5 years after treatment, with a peak incidence after 2 years. Therefore, during the follow-up period, patients undergo a series of ultrasound (US) and mammographic examinations. However, after surgery and radiation therapy, several modifications occur in the treated breast, causing difficulties in image interpretation, especially when local recurrence is suspected. Although not included in routine follow-up, magnetic resonance imaging (MRI) is often used in clinical practice, being considered more sensitive than the conventional imaging examinations in discriminating between postsurgical tissue modifications and tumor recurrence. In this review article, we analyze expected and pathologic breast MRI findings after conservative oncoplastic surgery compared to US and mammographic findings in order to distinguish local recurrence and avoid potential pitfalls in image interpretation.

Survival of preterm infants have dramatically improved over the last decades. Nonetheless, infants born preterm remain vulnerable to many complications, including necrotizing enterocolitis (NEC). The severity of the disease and the mortality rate are directly correlated with decreasing gestational age and birth weight. Despite surgical treatment mortality rate remains very high in extremely premature infants, especially in newborns at the lowest limit of viability. Survival of infants of birth weight (BW) below 750 g has been increasingly reported in recent years, however the overall mortality in extremely low "BW" infants (ELBW) requiring surgery for NEC has not decreased over the past years. We describe our experience with a male preterm infant who survived after an ileostomy procedure for Bell stage II NEC, with improving neuromotor skills at 2 years follow up. Although standard indication to surgery is Bell stage III, in our case the choice of minimal laparotomy, exploration of the bowel and ileostomy at Bell stage II was safe and effective. Our experience suggest that surgery has not a negative impact on survival and ileostomy could prevent further damage of the bowel in NEC. We hypothesize that indication to surgery at an earlier stage may prevent further progression of the disease without a significantly negative impact on survival. Further studies are needed to confirm the appropriateness of this approach in ELBW infants.

Despite the effectiveness of combined anti-retroviral therapy, human immunodeficiency virus (HIV) infected-patients frequently report diarrhea and neuropsychological deficits. It is claimed that the viral HIV-1 Trans activating factor (HIV-1 Tat) protein is responsible for both diarrhea and neurotoxic effects, but the underlying mechanisms are not known. We hypothesize that colonic application of HIV-1 Tat activates glial cells of the enteric nervous system (EGCs), leading to a neuroinflammatory response able to propagate to the central nervous system. We demonstrated that HIV-1 Tat-induced diarrhea was associated with a significant activation of glial cells within the colonic wall, the spinal cord and the frontal cortex, and caused a consistent impairment of the cognitive performances. The inhibition of glial cells activity by lidocaine, completely abolished the above-described effects. These observations point out the role of glial cells as putative effectors in HIV-1 Tat-associated gastrointestinal and neurological manifestations and key regulators of gut-brain signaling.

Galectin-3 (Gal-3) is an endogenous β-galactoside-binding lectin, playing an important role in the pathogenesis of multiple malignancies. Aim of the study was to evaluate in a group of patients treated for ovarian cancer (EOC), the role of Gal-3 combined with multi-detector contrast-enhanced computed tomography (MDCT), as predictor of recurrence disease. Seventeen follow-up patients with recurrent ovarian cancer and 13 follow-up patients with stable ovarian disease, who performed MDCT at one-year follow-up after cytoreductive treatment, were enrolled. Serum Gal-3 concentrations were determined by using ELISA method. Twenty healthy controls were included in the analysis. Two radiologist blinded to patients status, reviewed MDCT exams, recording the following signs of disease recurrence: local tumor spread, enlarged lymph-nodes, carcinomatosis implants and metastases. We calculated the respective threshold values of Gal- 3 identified by ROC curve analysis for each imaging findings related to disease recurrence : lymphoadenopathies 92.45 ng/ml (AUC: 0.81, Se=91% Spe=73%), carcinomatosis 85.95 ng/ml (AUC:0.93 Se= 93.7%, Spe=92.8%), local tumor spread 99.05 (AUC:0.90, Se=100%, Spe=73% ) and metastasis 99.05ng/ml (AUC :0,78, Se=100% , Spe=70%). A significant correlation between high Gal-3 serum levels and presence of local tumor spread (n=11/17, p:0.001), carcinomatosis (n=16/17, p:0.00), lymphoadenopathies (n=15/17, p:0.00) and metastasis (n=11/17, p:0.003) related with recurrence disease was observed. Patients with recurrence of ovarian cancer presents higher Gal-3 values compared to women with stable diseases. Gal-3 combined to CECT should be used to improve the monitoring of EOC patients., (Creative Commons Attribution License)

The objective of this study is to analyze magnetic resonance imaging shrinkage pattern of tumor regression after neoadjuvant chemotherapy and to evaluate its relationship with biological subtypes and pathological response. We reviewed the magnetic resonance imaging studies of 51 patients with single mass-enhancing lesions (performed at time 0 and at the II and last cycles of neoadjuvant chemotherapy). Tumors were classified as Luminal A, Luminal B, HER2+, and Triple Negative based on biological and immunohistochemical analysis after core needle biopsy. We classified shrinkage pattern, based on tumor regression morphology on magnetic resonance imaging at the II cycle, as concentric, nodular, and mixed. We assigned a numeric score (0: none; 1: low; 2: medium; 3: high) to the enhancement intensity decrease. Pathological response on the surgical specimen was classified as complete (grade 5), partial (grades 4-3), and non-response (grades 1-2) according to Miller and Payne system. Fisher test was used to relate shrinkage pattern with biological subtypes and final pathological response. Seventeen patients achieved complete response, 25 partial response, and 9 non-response. A total of 13 lesions showed nodular pattern, 20 concentric, and 18 mixed. We found an association between concentric pattern and HER2+ (p < 0.001) and mixed pattern and Luminal A lesions (p < 0.001). We observed a statistical significant correlation between concentric pattern and complete response (p < 0.001) and between mixed pattern and non-response (p = 0.005). Enhancement intensity decrease 3 was associated with complete response (p < 0.001). Shrinkage pattern and enhancement intensity decrease may serve as early response indicators after neoadjuvant chemotherapy. Shrinkage pattern correlates with tumor biological subtypes.

Activation of intestinal human pregnane X receptor (PXR) has recently been proposed as a promising strategy for the chemoprevention of inflammation-induced colon cancer. The present study was aimed at evaluating the effect of rifaximin, a non-absorbable antibiotic, in inhibiting angiogenesis in a model of human colorectal epithelium and investigating the role of PXR in its mechanism of action. Caco-2 cells were treated with rifaximin (0.1, 1.0 and 10.0 µM) in the presence or absence of ketoconazole (10 µM) and assessed for cell proliferation, migration and expression of proliferating cell nuclear antigen (PCNA). The release of vascular endothelial growth factor (VEGF) and nitric oxide (NO), expression of Akt, mechanistic target of rapamycin (mTOR), p38 mitogen activated protein kinases (MAPK), nuclear factor κB (NF-κB) and metalloproteinase-2 and -9 (MMP-2 and -9) were also evaluated. Treatment with rifaximin 0.1, 1.0 and 10.0 µM caused significant and concentration-dependent reduction of cell proliferation, cell migration and PCNA expression in the Caco-2 cells vs. untreated cells. Treatment downregulated VEGF secretion, NO release, VEGFR-2 expression, MMP-2 and MMP-9 expression vs. untreated cells. Rifaximin treatment also resulted in a concentration-dependent decrease in the phosphorylation of Akt, mTOR, p38MAPK and inhibition of hypoxia-inducible factor 1-α (HIF-1α), p70S6K and NF-κB. Ketoconazole (PXR antagonist) treatment inhibited these effects. These findings demonstrated that rifaximin causes PXR-mediated inhibition of angiogenic factors in Caco-2 cell line and may be a promising anticancer tool.